title: Peripheral endocannabinoid system dysregulation in first-episode psychosis.
abstract: Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) has a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been associated with psychosis. Cannabis use is a robust risk factor for these disorders that could alter the ECS signalling. In this study, 95 patients with a first episode of psychosis (FEP) and 90 healthy controls were recruited. Protein expression of cannabinoid receptor 2 (CB2), the protein levels of the main endocannabinoid synthesizing enzymes N-acyl phosphatidylethanolamine phospholipase (NAPE) and diacylglycerol lipase (DAGL), and of degradation enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were determined by western blot analysis in peripheral blood mononuclear cells (PBMCs). Patients with a FEP showed a decreased expression of CB2 and of both endocannabinoids synthesizing enzymes (NAPE and DAGL) in comparison to healthy controls. After controlling for age, gender, body mass index, and cannabis use, NAPE and DAGL expression remained significantly decreased, whereas FAAH and MAGL expression were increased. On the other hand, FEP subjects with history of severe cannabis use showed a larger ECS dysregulation compared with healthy controls. These results indicate an ECS dysregulation in PBMC of FEP patients. The alteration of the ECS presented at the initial phases of psychosis could be contributing to the pathophysiology of the disease and constitutes a possible biomarker of psychotic disorders and an interesting pharmacological target to take into account for therapeutic purposes.
authors.affiliation: Schizophrenia Clinic Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Bioque
authors.forename: Borja
authors.initials: B
authors.lastname: García-Bueno
authors.forename: Karina S
authors.initials: KS
authors.lastname: Macdowell
authors.forename: Ana
authors.initials: A
authors.lastname: Meseguer
authors.forename: Pilar A
authors.initials: PA
authors.lastname: Saiz
authors.forename: Mara
authors.initials: M
authors.lastname: Parellada
authors.forename: Ana
authors.initials: A
authors.lastname: Gonzalez-Pinto
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez-Jimenez
authors.forename: Antonio
authors.initials: A
authors.lastname: Lobo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
authors.forename: Miguel
authors.initials: M
authors.lastname: Bernardo
mesh_terms: D000293:Adolescent; D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism; D002648:Child; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000378:metabolism* / Q000473:pathology*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D008994:Monoacylglycerol Lipases; D010739:Phospholipase D; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C581518:NAPEPLD protein, human